Quimiocinas e receptores de quimiocinas na infecção pelo HIV : genética e imunologia na modulação da resposta imune em pacientes HIV+ com diferentes perfis de progressão da doença e após início dos antirretrovirais

Fatores genéticos e imunológicos influenciam as diferentes respostas observadas entre indivíduos, desde a exposição ao HIV até o desenvolvimento da aids. As quimiocinas e seus receptores atuam na comunicação entre o sistema imune inato e adaptativo após o estabelecimento da infecção. A variabilidade genética dessas moléculas pode ser essencial para a resposta imune, principalmente se essas moléculas agem na fase inicial da infecção, fase esta que definirá o transcurso da doença. Além disso, a investigação da expressão de quimiocinas nos diferentes estágios clínicos da infecção e sua modulação após iniciado o tratamento com ARVs (antirretrovirais) é importante na busca de biomarcadores. Neste estudo, exploramos o papel de quinze polimorfismos candidatos em genes de receptores de quimiocinas e seus ligantes na susceptibilidade e na progressão à aids. Além disso, foram quantificados os níveis plasmáticos de seis quimiocinas em progressores extremos nos diferentes estágios clínicos da infecção e avaliamos o impacto da terapia como moduladora da resposta imune. Os resultados nos mostram que os polimorfismos rs56061981 no CXCL10 (CT/TT, OR: 1,819, IC 95% 1,074-3,081, P=0,026) e rs3091250 no CCR3 (TT, OR: 2,147, IC 95% 1,076-4,287, P=0,030) influenciam na susceptibilidade à infecção pelo HIV. Nas análises de interação gene-gene realizadas por redução multifatorial de dimensionalidade (MDR), observou-se que o rs56061981 no CXCL10 e rs4359426 no CCL22, juntos predizem 57% da susceptibilidade à infecção pelo HIV (P=0,008). Ademais, observou-se que os polimorfismos rs13034664 no CCL20 (CC, OR: 0,214, IC 95% 0,063-0,730, P=0,014) e rs4359426 no CCL22 (CA/AA, OR: 2,685, IC 95% 1,128-6,392, P=0,026) foram associados com a progressão rápida à aids. Com relação aos níveis plasmáticos, o CXCL10 estava significativamente aumentado nos progressores rápidos (Pcorrigido(c)=0,003) e lentos (Pc≤0,0001) pré-aids quando comparado com os controles saudáveis. Neste contexto, sugere-se o CXCL10 como biomarcador em indivíduos crônicos HIV+. Quando avaliadas as subpopulações celulares T auxiliares em HIV+ sob ARV, se observou uma frequência aumentada de linfócitos TCD4+ ativados nos progressores rápidos (1,3% vs. 13,6%, Pc=0,008) e nos progressores lentos (1,3% vs. 5,4%, Pc=0,044) quando comparados com os controles saudáveis. Já a frequência de linfócitos T CD8+ ativados foi mais alta nos progressores rápidos quando comparados com os controles saudáveis (0,32% vs. 8,7%; Pc=0,001). A frequência de células Th2 estava diminuída nos progressores rápidos (Pc=0,027) e, nos progressores lentos, as células Th1 estavam com frequência diminuída, enquanto que a frequência das Th17 estava aumentada quando comparados com os controles saudáveis (Pc=0,007 e Pc=0,042, respectivamente), se observando um desequilíbrio de subconjuntos celulares T CD4+ nos progressores extremos sob ARV.From HIV exposition to AIDS disease different responses against HIV infection are influenced by immunological and genetic host factors. Chemokines and their receptors link the innate and adaptive system after the establishment of HIV infection. Genetic diversity of these molecules is crucial to the immune response, since they have a pivotal role in the early infection, clinical stage which predicts the disease progression. Furthermore, to investigate the expression of chemokines in different clinical stages of HIV infection and their modulation before and after initiated ART (antiretroviral therapy) is important to identify biomarkers of progression. In this study, we explored the role of 15 candidate polymorphisms in chemokine receptor and chemokine genes on susceptibility to HIV infection and progression to AIDS. Also, plasma levels of six chemokines were quantified in extreme progressors in different clinical stages of infection and the impact of ART, as a modulator of the immune response, was evaluated. The CXCL10 rs56061981 (CT/TT, OR: 1.819, CI 95% 1.074-3.081, P=0.026) and CCR3 rs3091250 (TT, OR: 2.147, CI 95% 1.076-4.287, P=0.030) variants were associated with susceptibility to HIV infection. Also, in the MDR (Multifactor Dimensionality Reduction) analyses, the best model to predict the susceptibility to HIV infection was composed by CXCL10 rs56061981 and CCL22 rs4359426 with 57% of accuracy (P=0.008). In analysis of disease progression, CCL20 rs13034664 (CC, OR: 0.214, CI 95% 0.063-0.730, P=0.014) and CCL22 rs4359426 (CA/AA, OR: 2.685, CI 95% 1.128-6.392, P=0.026) variants were associated with rapid progression to AIDS. Regarding plasma levels, CXCL10 levels were higher in rapid progressors (RPs) (Pcorrected(c)=0.003) and slow progressors (SPs) (Pc≤0.0001) in pre-AIDS when compared to healthy controls and this molecule was suggested as a potential biomarker of disease progression. Furthermore, frequencies of activated CD4+ T-cell were higher in SPs (1.3% vs. 5.4%, Pc=0.044) and RPs (1.3% vs. 13.6%, Pc=0.008) under ART when compared with healthy controls. On the other hand, frequencies of activated CD8+ T cell were elevated in RPs (0.32% vs. 8.7%, Pc=0.001) under ART when compared with controls. Th2 cell frequency was lower in RPs under ART (Pc=0.027) when compared with controls, and Th1 cell frequency was lower (Pc=0.007) and Th17 cells were higher (Pc=0.042) in SPs under ART when compared with healthy controls

Control and prevention of infectious diseases from a One Health perspective

The ongoing COVID-19 pandemic has caught the attention of the global community and rekindled the debate about our ability to prevent and manage outbreaks, epidemics, and pandemics. Many alternatives are suggested to address these urgent issues. Some of them are quite interesting, but with little practical application in the short or medium term. To realistically control infectious diseases, human, animal, and environmental factors need to be considered together, based on the One Health perspective. In this article, we highlight the most effective initiatives for the control and prevention of infectious diseases: vaccination; environmental sanitation; vector control; social programs that encourage a reduction in the population growth; control of urbanization; safe sex stimulation; testing; treatment of sexually and vertically transmitted infections; promotion of personal hygiene practices; food safety and proper nutrition; reduction of the human contact with wildlife and livestock; reduction of social inequalities; infectious disease surveillance; and biodiversity preservation. Subsequently, this article highlights the impacts of human genetics on susceptibility to infections and disease progression, using the SARS-CoV-2 infection as a study model. Finally, actions focused on mitigation of outbreaks and epidemics and the importance of conservation of ecosystems and translational ecology as public health strategies are also discussed

Beyond diversity loss and climate change : impacts of Amazon deforestation on infectious diseases and public health

Amazonian biodiversity is increasingly threatened due to the weakening of policies for combating deforestation, especially in Brazil. Loss of animal and plant species, many not yet known to science, is just one among many negative consequences of Amazon deforestation. Deforestation affects indigenous communities, riverside as well as urban populations, and even planetary health. Amazonia has a prominent role in regulating the Earth’s climate, with forest loss contributing to rising regional and global temperatures and intensification of extreme weather events. These climatic conditions are important drivers of emerging infectious diseases, and activities associated with deforestation contribute to the spread of disease vectors. This review presents the main impacts of Amazon deforestation on infectious-disease dynamics and public health from a One Health perspective. Because Brazil holds the largest area of Amazon rainforest, emphasis is given to the Brazilian scenario. Finally, potential solutions to mitigate deforestation and emerging infectious diseases are presented from the perspectives of researchers in different fields

Synthesizing the connections between environmental disturbances and zoonotic spillover

Zoonotic spillover is a phenomenon characterized by the transfer of pathogens between different animal species. Most human emerging infectious diseases originate from non-human animals, and human-related environmental disturbances are the driving forces of the emergence of new human pathogens. Synthesizing the sequence of basic events involved in the emergence of new human pathogens is important for guiding the understanding, identifi cation, and description of key aspects of human activities that can be changed to prevent new outbreaks, epidemics, and pandemics. This review synthesizes the connections between environmental disturbances and increased risk of spillover events based on the One Health perspective. Anthropogenic disturbances in the environment (e.g., deforestation, habitat fragmentation, biodiversity loss, wildlife exploitation) lead to changes in ecological niches, reduction of the dilution effect, increased contact between humans and other animals, changes in the incidence and load of pathogens in animal populations, and alterations in the abiotic factors of landscapes. These phenomena can increase the risk of spillover events and, potentially, facilitate new infectious disease outbreaks. Using Brazil as a study model, this review brings a discussion concerning anthropogenic activities in the Amazon region and their potential impacts on spillover risk and spread of emerging diseases in this region

Avaliação imunogenética de variantes dos receptores tipo toll 7, 8 e 9 em pacientes infectados pelo vírus da imunodeficiência humana tipo 1

Diferentes mecanismos envolvidos no controle da infecção pelo HIV-1 dependem, além de fatores virais, da variabilidade genética do hospedeiro. Assim, foi observado que os receptores tipo Toll (TLRs) endossomais, tais como TLR7, 8 e 9, estão envolvidos no reconhecimento de ácidos nucleicos derivados de vírus, como o HIV-1. Sendo que TLR7/8 reconhecem RNA simples fita (ssRNA) e TLR9 reconhece DNA dupla ou simples fita (ssDNA/dsDNA). Observou-se que o ssRNA derivado de HIV-1 é reconhecido pelos TLR7/8, os quais estimulam células dendríticas (DCs) e macrófagos à produção de interferons (IFNs) e citocinas pró-inflamatórias. Também foi observado que a proteína gp120 do HIV inibe a ativação das DCs plasmocitóides (pDCs), que expressam TLR9, consequentemente inibindo produção de IFN-α. Variantes nos genes TLR7/8/9 já foram associadas com a infecção ao HIV-1 e outras doenças inflamatórias, autoimunes e infecciosas. O objetivo deste estudo foi avaliar a influência dos polimorfismos genéticos potencialmente funcionais: rs179008 no TLR7, rs3764880 no TLR8, rs5743836 e rs352140 no TLR9 em 366 pacientes adultos HIV+ e 415 indivíduos adultos saudáveis provenientes do sul do Brasil. O polimorfismo rs5743836 do TLR9 foi genotipado através da técnica de PCR alelo específico BIPASA enquanto que os demais polimorfismos por PCR-RFLP. As frequências genotípicas e haplotípicas foram comparadas usando o teste de Qui-quadrado e as frequências alélicas usando o teste Exato de Fisher. As comparações foram realizadas subdividindo os indivíduos de acordo com a origem étnica e o sexo. Quando comparamos indivíduos HIV+ eurodescendentes com o grupo controle, observamos diferenças nas frequências alélicas e genotípicas para o polimorfismo rs5743836 no TLR9 (P=0,011 e P=0,028, respectivamente), sendo que a frequência do genótipo CC foi maior nos pacientes quando comparado com os controles (residual P=0,040) conferindo susceptibilidade à infecção (OR=1,53; 95% IC: 1,05-2,23; P=0,030, modelo dominante). Na comparação dos indivíduos HIV+ afrodescendentes com o grupo controle, houve uma menor frequência do genótipo TC nos pacientes (residual P=0,006), sendo que esse genótipo foi associado com proteção à infecção (OR=0,60; 95% IC: 0,36-0,99; P=0,049, modelo dominante). Na análise de haplótipos dos polimorfismos rs5743836 e rs352140 do TLR9, as frequências haplotípicas estimadas não foram diferentes na comparação entre pacientes e controles. Em relação aos polimorfismos do TLR7 e TLR8 também não observamos diferenças nas frequências alélicas e genotípicas quando comparamos pacientes e controles. Nossos resultados demonstram o papel fundamental do polimorfismo rs5743836 na infecção do HIV e a importância do background genético entre os grupos étnicos que influenciam na susceptibilidade frente ao vírus.Different mechanisms are involved in the control of HIV infection, as viral factors and genetic variability on the host. Thus, intracellular Toll-like receptors (TLRs), such as TLR7/8/9, are involved in the recognition of nucleic acids derived from viruses. TLR7/8 recognizes simple RNA strand (ssRNA) and TLR9 recognizes simple or double DNA strand (ss/dsDNA). It was showed that the ssRNA derived from HIV is recognized by TLR7/8 and stimulates DCs and macrophages to secrete IFN-α and proinflammatory cytokines. Also, a direct interaction of HIV gp120 with pDCs inhibits TLR9-mediated responses, including pDC activation and IFN-α secretion. TLR7/8/9 polymorphisms have been associated with HIV infection and other inflammatory autoimmune and infectious diseases. The aim of this study was to evaluate the influence of the rs179008 TLR7, rs3764880 TLR8 and rs5743836/rs352140 TLR9 polymorphisms, potentially functional, in 366 HIV+ adults patients and 415 healthy adults subjects from the Southern Brazil. The rs5743836 polymorphism was genotyped by allele specific PCR-BIPASA while the other variants by PCR-RFLP. Genotypic and haplotypic frequencies were compared using the Chi-square test and allele frequencies using the Fisher's exact test. The comparisons were made by subdividing the sample according to ethnicity and gender. In European-derived individuals, differences in genotypic and allelic frequencies was observed for the rs5743836 as compared patients with controls (P=0.028 and P=0.011, respectively). Also, a higher frequency for the CC genotype in patients as compared with controls (residual P=0.040), this genotype conferring susceptibility to HIV-1 infection (OR=1,53; 95% CI: 1,05-2,23; P=0,030, dominant model). In African-derived individuals, was observed that the rs5743836 TC genotype frequency was lower in patients as compared to controls (residual P=0,006) being associated with protection against to HIV infection (OR=0,60; 95% CI: 0,36-0,99; P=0,049). No differences in allelic and genotypic frequencies were observed for the TLR7/8 polymorphisms or haplotypic frequencies of TLR9 variants, comparing patients and controls. Our results suggest that the rs5743836 TLR9 polymorphism has an important role in HIV-1 infection since it was associated with susceptibility in Euro-derived and Afro-derived individuals. Keywords: TLRs, HIV-1, ethnicity, polymorphisms

Avaliação imunogenética de variantes dos receptores tipo toll 7, 8 e 9 em pacientes infectados pelo vírus da imunodeficiência humana tipo 1

Diferentes mecanismos envolvidos no controle da infecção pelo HIV-1 dependem, além de fatores virais, da variabilidade genética do hospedeiro. Assim, foi observado que os receptores tipo Toll (TLRs) endossomais, tais como TLR7, 8 e 9, estão envolvidos no reconhecimento de ácidos nucleicos derivados de vírus, como o HIV-1. Sendo que TLR7/8 reconhecem RNA simples fita (ssRNA) e TLR9 reconhece DNA dupla ou simples fita (ssDNA/dsDNA). Observou-se que o ssRNA derivado de HIV-1 é reconhecido pelos TLR7/8, os quais estimulam células dendríticas (DCs) e macrófagos à produção de interferons (IFNs) e citocinas pró-inflamatórias. Também foi observado que a proteína gp120 do HIV inibe a ativação das DCs plasmocitóides (pDCs), que expressam TLR9, consequentemente inibindo produção de IFN-α. Variantes nos genes TLR7/8/9 já foram associadas com a infecção ao HIV-1 e outras doenças inflamatórias, autoimunes e infecciosas. O objetivo deste estudo foi avaliar a influência dos polimorfismos genéticos potencialmente funcionais: rs179008 no TLR7, rs3764880 no TLR8, rs5743836 e rs352140 no TLR9 em 366 pacientes adultos HIV+ e 415 indivíduos adultos saudáveis provenientes do sul do Brasil. O polimorfismo rs5743836 do TLR9 foi genotipado através da técnica de PCR alelo específico BIPASA enquanto que os demais polimorfismos por PCR-RFLP. As frequências genotípicas e haplotípicas foram comparadas usando o teste de Qui-quadrado e as frequências alélicas usando o teste Exato de Fisher. As comparações foram realizadas subdividindo os indivíduos de acordo com a origem étnica e o sexo. Quando comparamos indivíduos HIV+ eurodescendentes com o grupo controle, observamos diferenças nas frequências alélicas e genotípicas para o polimorfismo rs5743836 no TLR9 (P=0,011 e P=0,028, respectivamente), sendo que a frequência do genótipo CC foi maior nos pacientes quando comparado com os controles (residual P=0,040) conferindo susceptibilidade à infecção (OR=1,53; 95% IC: 1,05-2,23; P=0,030, modelo dominante). Na comparação dos indivíduos HIV+ afrodescendentes com o grupo controle, houve uma menor frequência do genótipo TC nos pacientes (residual P=0,006), sendo que esse genótipo foi associado com proteção à infecção (OR=0,60; 95% IC: 0,36-0,99; P=0,049, modelo dominante). Na análise de haplótipos dos polimorfismos rs5743836 e rs352140 do TLR9, as frequências haplotípicas estimadas não foram diferentes na comparação entre pacientes e controles. Em relação aos polimorfismos do TLR7 e TLR8 também não observamos diferenças nas frequências alélicas e genotípicas quando comparamos pacientes e controles. Nossos resultados demonstram o papel fundamental do polimorfismo rs5743836 na infecção do HIV e a importância do background genético entre os grupos étnicos que influenciam na susceptibilidade frente ao vírus.Different mechanisms are involved in the control of HIV infection, as viral factors and genetic variability on the host. Thus, intracellular Toll-like receptors (TLRs), such as TLR7/8/9, are involved in the recognition of nucleic acids derived from viruses. TLR7/8 recognizes simple RNA strand (ssRNA) and TLR9 recognizes simple or double DNA strand (ss/dsDNA). It was showed that the ssRNA derived from HIV is recognized by TLR7/8 and stimulates DCs and macrophages to secrete IFN-α and proinflammatory cytokines. Also, a direct interaction of HIV gp120 with pDCs inhibits TLR9-mediated responses, including pDC activation and IFN-α secretion. TLR7/8/9 polymorphisms have been associated with HIV infection and other inflammatory autoimmune and infectious diseases. The aim of this study was to evaluate the influence of the rs179008 TLR7, rs3764880 TLR8 and rs5743836/rs352140 TLR9 polymorphisms, potentially functional, in 366 HIV+ adults patients and 415 healthy adults subjects from the Southern Brazil. The rs5743836 polymorphism was genotyped by allele specific PCR-BIPASA while the other variants by PCR-RFLP. Genotypic and haplotypic frequencies were compared using the Chi-square test and allele frequencies using the Fisher's exact test. The comparisons were made by subdividing the sample according to ethnicity and gender. In European-derived individuals, differences in genotypic and allelic frequencies was observed for the rs5743836 as compared patients with controls (P=0.028 and P=0.011, respectively). Also, a higher frequency for the CC genotype in patients as compared with controls (residual P=0.040), this genotype conferring susceptibility to HIV-1 infection (OR=1,53; 95% CI: 1,05-2,23; P=0,030, dominant model). In African-derived individuals, was observed that the rs5743836 TC genotype frequency was lower in patients as compared to controls (residual P=0,006) being associated with protection against to HIV infection (OR=0,60; 95% CI: 0,36-0,99; P=0,049). No differences in allelic and genotypic frequencies were observed for the TLR7/8 polymorphisms or haplotypic frequencies of TLR9 variants, comparing patients and controls. Our results suggest that the rs5743836 TLR9 polymorphism has an important role in HIV-1 infection since it was associated with susceptibility in Euro-derived and Afro-derived individuals. Keywords: TLRs, HIV-1, ethnicity, polymorphisms

Quimiocinas e receptores de quimiocinas na infecção pelo HIV : genética e imunologia na modulação da resposta imune em pacientes HIV+ com diferentes perfis de progressão da doença e após início dos antirretrovirais

Fatores genéticos e imunológicos influenciam as diferentes respostas observadas entre indivíduos, desde a exposição ao HIV até o desenvolvimento da aids. As quimiocinas e seus receptores atuam na comunicação entre o sistema imune inato e adaptativo após o estabelecimento da infecção. A variabilidade genética dessas moléculas pode ser essencial para a resposta imune, principalmente se essas moléculas agem na fase inicial da infecção, fase esta que definirá o transcurso da doença. Além disso, a investigação da expressão de quimiocinas nos diferentes estágios clínicos da infecção e sua modulação após iniciado o tratamento com ARVs (antirretrovirais) é importante na busca de biomarcadores. Neste estudo, exploramos o papel de quinze polimorfismos candidatos em genes de receptores de quimiocinas e seus ligantes na susceptibilidade e na progressão à aids. Além disso, foram quantificados os níveis plasmáticos de seis quimiocinas em progressores extremos nos diferentes estágios clínicos da infecção e avaliamos o impacto da terapia como moduladora da resposta imune. Os resultados nos mostram que os polimorfismos rs56061981 no CXCL10 (CT/TT, OR: 1,819, IC 95% 1,074-3,081, P=0,026) e rs3091250 no CCR3 (TT, OR: 2,147, IC 95% 1,076-4,287, P=0,030) influenciam na susceptibilidade à infecção pelo HIV. Nas análises de interação gene-gene realizadas por redução multifatorial de dimensionalidade (MDR), observou-se que o rs56061981 no CXCL10 e rs4359426 no CCL22, juntos predizem 57% da susceptibilidade à infecção pelo HIV (P=0,008). Ademais, observou-se que os polimorfismos rs13034664 no CCL20 (CC, OR: 0,214, IC 95% 0,063-0,730, P=0,014) e rs4359426 no CCL22 (CA/AA, OR: 2,685, IC 95% 1,128-6,392, P=0,026) foram associados com a progressão rápida à aids. Com relação aos níveis plasmáticos, o CXCL10 estava significativamente aumentado nos progressores rápidos (Pcorrigido(c)=0,003) e lentos (Pc≤0,0001) pré-aids quando comparado com os controles saudáveis. Neste contexto, sugere-se o CXCL10 como biomarcador em indivíduos crônicos HIV+. Quando avaliadas as subpopulações celulares T auxiliares em HIV+ sob ARV, se observou uma frequência aumentada de linfócitos TCD4+ ativados nos progressores rápidos (1,3% vs. 13,6%, Pc=0,008) e nos progressores lentos (1,3% vs. 5,4%, Pc=0,044) quando comparados com os controles saudáveis. Já a frequência de linfócitos T CD8+ ativados foi mais alta nos progressores rápidos quando comparados com os controles saudáveis (0,32% vs. 8,7%; Pc=0,001). A frequência de células Th2 estava diminuída nos progressores rápidos (Pc=0,027) e, nos progressores lentos, as células Th1 estavam com frequência diminuída, enquanto que a frequência das Th17 estava aumentada quando comparados com os controles saudáveis (Pc=0,007 e Pc=0,042, respectivamente), se observando um desequilíbrio de subconjuntos celulares T CD4+ nos progressores extremos sob ARV.From HIV exposition to AIDS disease different responses against HIV infection are influenced by immunological and genetic host factors. Chemokines and their receptors link the innate and adaptive system after the establishment of HIV infection. Genetic diversity of these molecules is crucial to the immune response, since they have a pivotal role in the early infection, clinical stage which predicts the disease progression. Furthermore, to investigate the expression of chemokines in different clinical stages of HIV infection and their modulation before and after initiated ART (antiretroviral therapy) is important to identify biomarkers of progression. In this study, we explored the role of 15 candidate polymorphisms in chemokine receptor and chemokine genes on susceptibility to HIV infection and progression to AIDS. Also, plasma levels of six chemokines were quantified in extreme progressors in different clinical stages of infection and the impact of ART, as a modulator of the immune response, was evaluated. The CXCL10 rs56061981 (CT/TT, OR: 1.819, CI 95% 1.074-3.081, P=0.026) and CCR3 rs3091250 (TT, OR: 2.147, CI 95% 1.076-4.287, P=0.030) variants were associated with susceptibility to HIV infection. Also, in the MDR (Multifactor Dimensionality Reduction) analyses, the best model to predict the susceptibility to HIV infection was composed by CXCL10 rs56061981 and CCL22 rs4359426 with 57% of accuracy (P=0.008). In analysis of disease progression, CCL20 rs13034664 (CC, OR: 0.214, CI 95% 0.063-0.730, P=0.014) and CCL22 rs4359426 (CA/AA, OR: 2.685, CI 95% 1.128-6.392, P=0.026) variants were associated with rapid progression to AIDS. Regarding plasma levels, CXCL10 levels were higher in rapid progressors (RPs) (Pcorrected(c)=0.003) and slow progressors (SPs) (Pc≤0.0001) in pre-AIDS when compared to healthy controls and this molecule was suggested as a potential biomarker of disease progression. Furthermore, frequencies of activated CD4+ T-cell were higher in SPs (1.3% vs. 5.4%, Pc=0.044) and RPs (1.3% vs. 13.6%, Pc=0.008) under ART when compared with healthy controls. On the other hand, frequencies of activated CD8+ T cell were elevated in RPs (0.32% vs. 8.7%, Pc=0.001) under ART when compared with controls. Th2 cell frequency was lower in RPs under ART (Pc=0.027) when compared with controls, and Th1 cell frequency was lower (Pc=0.007) and Th17 cells were higher (Pc=0.042) in SPs under ART when compared with healthy controls

New Insights about Treg and Th17 Cells in HIV Infection and Disease Progression

Treg and Th17 cell subsets are characterized by the expression of specific transcriptional factors and chemokine receptor as well as by secretion of specific cytokine and chemokines. These subsets are important to the differentiation, expansion, homing capacity, and recruitment of several different immune cell populations to the site of infection. Whereas Treg cells maintain self-tolerance and control the activation and expansion of autoreactive CD4+ T effector cells through an anti-inflammatory response, Th17 cells, in an exacerbated unregulated proinflammatory response, can promote autoimmunity. Despite such apparently opposite functions, Th17 and Treg cells share common characteristics, and their differentiation pathways are interconnected. Recent studies have revealed quite intricate relations between Treg and Th17 cells in HIV infection and progression to AIDS. Considering Treg cells, different subsets were already investigated in the context of HIV infection, indicating a fluctuation in the total number and frequency throughout the disease course. This review focuses on the recent findings regarding the role of regulatory T and Th17 cells in the context of HIV infection, highlighting the importance of the balance between these two subsets on disease progression

Beyond diversity loss and climate change : impacts of Amazon deforestation on infectious diseases and public health

Amazonian biodiversity is increasingly threatened due to the weakening of policies for combating deforestation, especially in Brazil. Loss of animal and plant species, many not yet known to science, is just one among many negative consequences of Amazon deforestation. Deforestation affects indigenous communities, riverside as well as urban populations, and even planetary health. Amazonia has a prominent role in regulating the Earth’s climate, with forest loss contributing to rising regional and global temperatures and intensification of extreme weather events. These climatic conditions are important drivers of emerging infectious diseases, and activities associated with deforestation contribute to the spread of disease vectors. This review presents the main impacts of Amazon deforestation on infectious-disease dynamics and public health from a One Health perspective. Because Brazil holds the largest area of Amazon rainforest, emphasis is given to the Brazilian scenario. Finally, potential solutions to mitigate deforestation and emerging infectious diseases are presented from the perspectives of researchers in different fields